The overall objective of this proposal is to gain greater insight into our dramatic finding that "Cortical" neurons express the protein and mRNA for the NGF receptor in normal aged and Alzheimer's brain. We propose experiments that are expected to answer questions concerning their laminar and topographic distribution, cell type, gene expression, cytoskeletal characteristics, relationship to areas displaying severe AD-like pathology in selected areas of neo and limbic cortex in normal aged and diseased brain. The planned studies will utilize immunocytochemistry with mono and polyclonal antibodies and in situ hybridization. The present striking observation that in both extreme old age and Alzheimer's disease a population of cortical neurons express the receptor for NGF suggests that the normally high levels of this trophic factor found in cortex may be involved in a process aimed at rescuing aged, dying or diseased neurons in both normal aging and Alzheimer's disease. Thus, the information gained from the proposed studies may indicate that NGF not only may be important for neuronal survival in AD but may be beneficial as a treatment for retarding the consequences of normal aging.